DESCRIPTION: (Applicant's Abstract) The long-term objective of this research is the effective and efficient synthesis of enantiomerically pure, biomedically important compounds by carbene methodologies that employ chiral dirhodium(II) or copper(I) catalysts. Carbene methodologies offer a spectrum of pathways for carbon-carbon bond formation extending from addition to insertion and ylide generation/rearrangement that have been used for the construction of lignans, 2-deoxyxylolactone, and a variety of lactones and lactams in high enantiomeric excess (94 percent or more ee) with exceptional diastereo-, regio-, and chemoselectivity. We have designed and synthesized four classes of dirhodium(II) carboxamidates whose reactivities and selectivities offer unique advantages to asymmetric syntheses that involve metal carbene intermediates, and a further expansion in catalyst capabilities is anticipated. Chiral copper catalysts, mainly based on chiral bis-oxazoline ligands, will also be evaluated. New methods are proposed for the highly selective synthesis of acetal-protected 2-deoxyxylolactone and 2-deoxyribonolactone, substituted derivatives, and their aza-sugar analogs via C-H insertion. This same transformation will be the core for the synthesis of imperanene, which shows aggregation inhibitory activity. Metal-assisted ylide generation and rearrangement will be directed to the asymmetric synthesis of multifunctional/multisubstituted amino acids as well as to lignans having a hydroxyl group at the alpha position, such as trachelogenin and wikstromol whose biological effects are reported to be intriguing. Ylide generation within peptides and proteins will be investigated to determine selectivity, local or remote. Macrocyclic cyclopropanation, a new and exceptionally facile methodology, offers convenient entry to casbene as well as to the diterpenoid lactones pinnatin A and pinnatin B which are cancer cell cytotoxins. Tandem reactions of bis-diazoesters either via cyclopropanation or insertion affords the opportunity to achieve complex syntheses with exacting selectivity that includes double diastereoselection (up to 99.4 percent ee). Finally, enantioselective cyclopropanation with diazo-methane, which has been elusive, will be examined in critical detail using chiral copper(I) and dirhodium(II) catalysts.